Evaluation of Bazedoxifene/Conjugated Estrogens for the Treatment of Menopausal Symptoms and Effects on Metabolic Parameters and Overall Safety Profile

Abstract

Preclinical and clinical data on bazedoxifene (BZA), a new selective estrogen receptor modulator, showed that it prevented bone loss in postmenopausal women and suggested the added benefit of reducing vasomotor symptoms while minimizing or antagonizing stimulatory effects on the breast and uterus. In the efficacy phase of the Selective estrogens, Menopause, and Response to Therapy-1 trial, the results of which were summarized in the previous abstract, combination of BZA with conjugated estrogens (CEs) in a tissue-selective estrogen complex prevented bone loss in postmenopausal women. The present study, also part of the Selective estrogens, Menopause, and Response to Therapy-1 trial, was a multicenter, double-blind, placebo-, and active phase 3 trial evaluating the effects of BZA/CE on menopausal symptoms, metabolic parameters, and the overall safety profile in postmenopausal women. The participants were 3397 healthy postmenopausal women with an intact uterus who were receiving hormone therapy. Women were randomly assigned to receive single daily oral doses of 6 BZA/CE regimens (BZA [10, 20, or 40 mg], each with CE [0.625 or 0.45 mg]), raloxifene 60 mg or placebo for up to 2-years. Compared to the placebo, the BZA (20 mg)/CE (0.625 or 0.45 mg) regimen significantly reduced the frequency and severity of hot flushes and improved parameters of vaginal atrophy. All BZA/CE doses reduced the daily number of hot flushes at 12 weeks by at least 3-fold compared to the placebo (51.7%–85.7% vs. 17.1%). Two BZA/CE regimens (BZA 20 mg/CE 0.625 or 0.45 mg) were significantly more effective than placebo in reducing both the frequency and severity of hot flushes. All dose levels of BZA/CE were associated with improved lipid and homocysteine parameters but had no significant effect on carbohydrate metabolism. Overall changes in coagulation parameters were similar for the placebo and BZA/CE. No apparent differences were found between the BZA/CE and placebo with respect to breast pain and overall adverse events. These findings indicate that a tissue-selective estrogen complex combining BZA and CE is effective in treating symptoms associated with menopause, especially vasomotor symptoms and vaginal atrophy, without increasing the incidence of breast pain or overall adverse reactions.